Jaundice is the most common condition that requires urgent medical attention in some newborns and is the result of elevation in circulating unconjugated bilirubin. The unbound unconjugated bilirubin can be specifically neurotoxic and, if untreated, is associated with irreversible lifelong neurological damage. This condition is the most easily preventable cause of brain damage in otherwise healthy infants. Thus, severe neonatal hyperbilirubinemia has been nominated for inclusion on the uniform newborn screening panel in the US. Two main reasons dictate that the screening should be performed at the point of care. First, bilirubin is light-sensitive, requiring immediate sample analysis and therefore not compatible with the traditional dried blood spot newborn screening paradigm. Second, neonates with severe hyperbilirubinemia need to be treated urgently often prior to discharge. Newborn screening, as currently performed by collecting dried blood spots from infants and then sending them to a centralized laboratory for analysis, with turnaround times of at least 3 days is not suitable for universal bilirubin screening. Therefore, there is an immediate need to develop novel point of care technologies that will meet the American Academy of Pediatrics recommendation for bilirubin screening. Advanced Liquid Logic's digital microfluidic platform is a recognized innovative, low-cost, automated microdroplet-based liquid handling system that can be configured to address this challenge. The digital microfluidic technology enables miniaturization of assays and significantly reduces reagent and sample volumes, lowering not only the costs but also the neonatal sample volume requirements. A disposable lab-on- a-chip will be developed to assess an infant's risk for developing bilirubin-induced neurotoxicity at the point of care. The proposed platform will multiplex assays to measure total serum biliruibin, unbound bilirubin, albumin and carboxyhemoglobin levels to screen for risks related to severe neonatal hyperbilirubinemia, as well as the most frequent, known cause of kernicterus, glucose-6-phosphate (G6PD) dehydrogenase deficiency. In collaboration with Duke and Stanford University, work is ongoing to measure total serum bilirubin and G6PD deficiency on the digital microfluidic platform. In this project, assays will be developed for unbound bilirubin, albumin, and carboxyhemoglobin in the digital microfluidic format and results will be compared with those obtained using standard laboratory methods at Duke University.